serval:BIB_FC33042A8239
Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose.
10.1007/s00262-011-1140-1
000304621900007
22080404
Lövgren
T.
author
Baumgaertner
P.
author
Wieckowski
S.
author
Devêvre
E.
author
Guillaume
P.
author
Luescher
I.
author
Rufer
N.
author
Speiser
D.E.
author
article
2012
Cancer Immunology, Immunotherapy
1432-0851
0340-7004
journal
61
6
817-826
In mice, vaccination with high peptide doses generates higher frequencies of specific CD8+ T cells, but with lower avidity compared to vaccination with lower peptide doses. To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant. Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups. Also, CD8+ T cell differentiation and cytokine production ex vivo were similar in the two groups. Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo. In accordance, CD8+ T cell clones derived from low peptide dose-vaccinated patients showed significantly increased degranulation and stronger cytotoxicity. In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers. Furthermore, CD8+ T cell clones from low peptide dose-vaccinated patients bound CD8 binding-deficient tetramers more efficiently, suggesting that they may express higher affinity TCRs. We conclude that low peptide dose vaccination generated CD8+ T cell responses with stronger cytotoxicity and lower CD8 dependence.
Cancer Vaccines/administration & dosage
Cancer Vaccines/immunology
Chemotherapy, Adjuvant
Cytokines/biosynthesis
Dose-Response Relationship, Drug
Female
HLA-A2 Antigen/immunology
Humans
MART-1 Antigen/immunology
Male
Melanoma/immunology
Melanoma/pathology
Neoplasm Staging
Oligodeoxyribonucleotides/administration & dosage
Oligodeoxyribonucleotides/immunology
Peptides/administration & dosage
Peptides/immunology
T-Lymphocytes, Cytotoxic/immunology
Vaccination
eng
60_published
true
Publication types: Journal Article ; Research Support, Non-U.S. Gov't Publication Status: ppublish
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